The judgment that imaging studies were over-utilised (1) should not be based on the degree of compliance with the Wells clinical decision rule (CDR), given the fact that the Wells score is not necessarily the optimal one for PE. In a study which compared 7 CDRs, namely, the Wells score, simplified Wells score, original Geneva score, revised Geneva score, Charlotte score and the Pisa model, diagnostic accuracy amounted to 0.44, 0.61, and 0.76 for simplified Wells score, Wells score, and Pisa model, respectively (2). The Wells score was tested in 598 primary care patients presenting with symptoms including cough, unexpected or sudden dyspnoea, deterioration in existing dyspnoea, and pleuritic pain, singly or in combination. These patients were referred to secondary care with suspected PE, where they were subsequently rigorously evaluated and investigated according to hospital guidelines. The diagnosis of PE was subsequently confirmed in 73 cases. However, in as many as 44 of those cases where PE was ruled out, the presenting Wells score amounted to >4 points (3), a score that is taken to signify "PE likely" in the simplified Wells score. In the evaluation of PE diagnostic confusion is compounded by the fact that PE can be an incidental finding, for example, during CT imaging in the oncological context (4). In the latter study, 25% of 52 patients with incidental PE had no PE-related symptoms (4). In the entire group of 52 patients with incidental PE, eight had m...
The judgment that imaging studies were over-utilised (1) should not be based on the degree of compliance with the Wells clinical decision rule (CDR), given the fact that the Wells score is not necessarily the optimal one for PE. In a study which compared 7 CDRs, namely, the Wells score, simplified Wells score, original Geneva score, revised Geneva score, Charlotte score and the Pisa model, diagnostic accuracy amounted to 0.44, 0.61, and 0.76 for simplified Wells score, Wells score, and Pisa model, respectively (2). The Wells score was tested in 598 primary care patients presenting with symptoms including cough, unexpected or sudden dyspnoea, deterioration in existing dyspnoea, and pleuritic pain, singly or in combination. These patients were referred to secondary care with suspected PE, where they were subsequently rigorously evaluated and investigated according to hospital guidelines. The diagnosis of PE was subsequently confirmed in 73 cases. However, in as many as 44 of those cases where PE was ruled out, the presenting Wells score amounted to >4 points (3), a score that is taken to signify "PE likely" in the simplified Wells score. In the evaluation of PE diagnostic confusion is compounded by the fact that PE can be an incidental finding, for example, during CT imaging in the oncological context (4). In the latter study, 25% of 52 patients with incidental PE had no PE-related symptoms (4). In the entire group of 52 patients with incidental PE, eight had main pulmonary artery thrombi, 19 had lobar thrombi, 11 had segmental thrombi, and 14 had subsegmental thrombi (4).
References
(1) Dhakal P., Iftikhar MH., Wang L., Atti V., Panthi S., Ling X et al
Overutilisation of imaging studies for diagnosis of pulmonary embolism: are we following the guidelines?
Postgrad Med J Jan 2019 doi;10.1136/postgradmedj-2018-135995
(2)Wahsh RA,, Agha MA Clinical probability of pulmonary embolism: comparison of different scoring systems
Egyptian Journal of Chest Diseases and Tuberculosis 2012;61:4190424
(3)Erkens PMG., Lucassen WAM., Geerding G-J., van Weert HCP., Kuijs-Augustijn M., van Heugten M et al
Alternative diagnoses in patients in whom the GP considered the diagnosis of pulmonary embolism
Family Practice 2014;31:670-677
(4)O'Connell CL., Boswell WD., Duddalwar V., Canton A., Mark LS., Vigen C., Liebman HA
Unsuspected pulmonary emboli in cancer patients: Clinical correlates and relevance
Journal of Clinical Oncology 2006;24:4828-4832
The terminology of the chest x-ray report can, indeed, impact on the timeliness of the eventual validation of the diagnosis of pulmonary tuberculosis, as shown by the case report of a 75 year old man who was originally admitted with fever and backache. Chest x-ray showed "fibronodular infiltration of the left apex of the lung" (1). On the basis of magnetic resonance imaging, backache was attributed to osteomyelitis, and he was treated with antibiotics, and there was no "work-up" of the fibronodular infiltration of the lung apex. Over a period of two weeks fever persisted, and he became pancytopenic. However, it was only after a further 3 weeks, when pancytopenia became more severe, that bone marrow aspiration and bone marrow biopsy was performed. The latter showed epitheloid granulomas and acid fast bacilli. Polymerase chain reaction analysis of the bone marrow specimens was positive for M tuberculosis DNA, and his sputum was culture positive for M tuberculosis. Although antituberculous chemotherapy was initiated immediately after the bone marrow results he died 3 days after commencing treatment (2).
Comment
Arguably, if the term "tuberculosis" had been used to qualify the nodular infiltration seen on chest x-ray, that would have raised the index of suspicion for tuberculosis (TB), and computed tomography might have been utilised to characterise the nodularity as being TB-related (2). Two weeks later, in the light of that heightene...
The terminology of the chest x-ray report can, indeed, impact on the timeliness of the eventual validation of the diagnosis of pulmonary tuberculosis, as shown by the case report of a 75 year old man who was originally admitted with fever and backache. Chest x-ray showed "fibronodular infiltration of the left apex of the lung" (1). On the basis of magnetic resonance imaging, backache was attributed to osteomyelitis, and he was treated with antibiotics, and there was no "work-up" of the fibronodular infiltration of the lung apex. Over a period of two weeks fever persisted, and he became pancytopenic. However, it was only after a further 3 weeks, when pancytopenia became more severe, that bone marrow aspiration and bone marrow biopsy was performed. The latter showed epitheloid granulomas and acid fast bacilli. Polymerase chain reaction analysis of the bone marrow specimens was positive for M tuberculosis DNA, and his sputum was culture positive for M tuberculosis. Although antituberculous chemotherapy was initiated immediately after the bone marrow results he died 3 days after commencing treatment (2).
Comment
Arguably, if the term "tuberculosis" had been used to qualify the nodular infiltration seen on chest x-ray, that would have raised the index of suspicion for tuberculosis (TB), and computed tomography might have been utilised to characterise the nodularity as being TB-related (2). Two weeks later, in the light of that heightened index of suspicion for TB, the subsequent development of pancytopenia might have raised the index of suspicion for disseminated tuberculosis, and bone marrow studies would have been initiated at that stage. Instead there was a further 3 weeks delay before the appropriate work-up for TB "kicked in" (1).
In the United States it is already recognised that delays in diagnosis of pulmonary TB are, in part, responsible for the paradox whereby population subgroups, such as white Americans, those in employment, and the US-born (all of them with background pulmonary TB rates of < 2 per 100,000 of the 2006 population) had higher 13-year increases in prevalence of cavitating tuberculosis than counterparts with higher background pulmonary TB rate (3). Might this phenomenon be attributable to greater prevalence of non-specific characterisation of chest x-ray images antedating cavitation in white, affluent, US-born citizens?
References
(1) Chien C-C., Chiou T-J., Lee M-Y., Hsiao L-T., Kwang W-K
Tuberculosis associated hemopahgocytic syndrome in a hemodialysis patient with protracted fever
International Journal of Hematology 2004;79:334-336
(2) Yoy M., Ellis S
Radiological diagnosis and follow up of pulmonary tuberculosis
Thorax 2010;86;663-674
(3)Wallace RM., Kammerer JS., Iademarco MF. et al
Increasing proportions of advanced pulmonary tuberculosis reported in the United States. Are delays in diagnosis on the rise?
Am J Respir Crit Care Med 2009;180:1016-1022
Given the fact that the risk of heparin-induced thrombocytopenia (HIT) is higher with prolonged therapy, the new oral anticoagulants (NOACs) might have a role in shortening the duration of low molecular weight heparin (LMWH) thromboprophylaxis in cancer patients from its currently recommended minimum of 3 months (1) to a much shorter duration by facilitating a transition to NOACSs( 2). That strategy might mitigate the risk of occurrence of HIT.
Currently, international guidelines recommend LMWH instead of warfarin for management of cancer-related venous thromboembolism (1), but the duration of that management strategy puts patients at risk of HIT, with all its attendant consequences. In an open-label, noninferiority trial, patients with cancer-associated venous thromboembolism were randomly assigned to LMWH for at least 5 days followed by oral edoxaban (60 mg/day) (edoxaban group) or subcutaneous dalteparin at an appropriate dose. Treatment duration in both cases was at least 6 months. In that study, recurrent venous thromboembolism occurred in 7.9% of the edoxaban group vs. 11.3% of the dalteparin group (P=0.09). Major bleeding occurred in 6.9% of the edoxaban group vs. 4% of the dalteparin group (P=0.04). The increase in major bleeding was principally attributable to upper gastrointestinal bleeding in patients who had gastric cancer (2). A criticism of that study is that the 60 mg/day of edoxaban is inherently associated with significantly (P=0.03) greater risk of...
Given the fact that the risk of heparin-induced thrombocytopenia (HIT) is higher with prolonged therapy, the new oral anticoagulants (NOACs) might have a role in shortening the duration of low molecular weight heparin (LMWH) thromboprophylaxis in cancer patients from its currently recommended minimum of 3 months (1) to a much shorter duration by facilitating a transition to NOACSs( 2). That strategy might mitigate the risk of occurrence of HIT.
Currently, international guidelines recommend LMWH instead of warfarin for management of cancer-related venous thromboembolism (1), but the duration of that management strategy puts patients at risk of HIT, with all its attendant consequences. In an open-label, noninferiority trial, patients with cancer-associated venous thromboembolism were randomly assigned to LMWH for at least 5 days followed by oral edoxaban (60 mg/day) (edoxaban group) or subcutaneous dalteparin at an appropriate dose. Treatment duration in both cases was at least 6 months. In that study, recurrent venous thromboembolism occurred in 7.9% of the edoxaban group vs. 11.3% of the dalteparin group (P=0.09). Major bleeding occurred in 6.9% of the edoxaban group vs. 4% of the dalteparin group (P=0.04). The increase in major bleeding was principally attributable to upper gastrointestinal bleeding in patients who had gastric cancer (2). A criticism of that study is that the 60 mg/day of edoxaban is inherently associated with significantly (P=0.03) greater risk of gastrointestinal bleeding (GIB) than vitamin K antagonists (VKA) therapy, but apixaban does not incur greater risk in that respect (3). For those patients who are eligible for the 30 mg/day dose of edoxaban, that preparation is an even better choice because it is associated with a significantly (p<0.001) lower risk of GIB than VKAs (3). Arguably, a NOAC with lower risk of GIB than VKAs might have a correspondingly lower risk of GIB than LWMH, but that hypothesis needs validating. Nevertheless, arguably with that hypothesis in mind, Al-Samkari et al. proposed a strategy for use of NOACs in cancer-related venous thromboembolism, whereby the most eligible patients would be those with no gastrointestinal malignancy, low risk of major bleeding, and no strong drug-drug interactions, especially if ease of treatment was a priority for that patient (4). I would add "especially if avoidance of HIT was also a priority".
References
(1)Farge D., Debourdeau P., Beckers P et al
International clinical practice guidelines for treatment and prophylaxis of venous thromboembolism in patients with cancer
J Thromb. Haemostat 2013;11:56-70
(2)Raskob GE., van Es N., Verhamme P et al
Edoxaban for the treatment of cancer-associated venous thromboembolism
N Engl J Med 2018;378:615-624
(3)Eikelboom J., Merli G
Bleeding with direct oral anticoagulants vs warfarin: Clinical experience
Am J Med 2016;129:S33-S40
(4)Al-Samkari H., Connors JM
The role of direct oral anticoagulants in treatment of cancer-associated thrombosis
Cancers 2018;10:271;doi:10.3390/cancers10080271
In their excellent review the authors drew attention to alternative oral anticoagulants to manage heparin-induced thrombocytopenia(HIT)(1). The American College of Chest Physicians guideline for HIT and HIT-associated thrombosis(HITT) cautions against premature transition to vitamin K antagonist therapy due to significant risk of warfarin-induced skin necrosis or development of venous limb gangrene(2). According to a recent review, the new oral anticoagulants(NOACs) are not burdened with that disadvantage, and their rapid onset of action generates a smooth transition to forward anticoagulation in patients with HIT/HITT. Furthermore, NOACs do not cross-react with HIT antibodies(3). That review encompassed data from 56 HIT/HITT patients subsequently treated with NOACs. Data were derived from 3 studies and 8 case reports. Mean age of the 56 patients was 70, twenty four had HIT, and thirty two had HITT. At the time of HIT/HITT diagnosis a nonheparin parenteral agent was initiated in 42, and the remaining 14 transitioned to NOACs straightaway. The NOACS used in the 56 patients were rivaroxaban, apixaban, and dabigatran in 54%, 29%, and 18% of cases, respectively. There were only 2 instances of recurrent thrombosis with NOAC therapy. Major bleeding occurred in 3 patients who did not appear to be on NOAC therapy at the time of the bleed.
References
(1) Prince M., Wenham T
Heparin-induced thrombocytopemia
Postgrad Med J 2018;94:453-547
(2)Linkins L-A....
In their excellent review the authors drew attention to alternative oral anticoagulants to manage heparin-induced thrombocytopenia(HIT)(1). The American College of Chest Physicians guideline for HIT and HIT-associated thrombosis(HITT) cautions against premature transition to vitamin K antagonist therapy due to significant risk of warfarin-induced skin necrosis or development of venous limb gangrene(2). According to a recent review, the new oral anticoagulants(NOACs) are not burdened with that disadvantage, and their rapid onset of action generates a smooth transition to forward anticoagulation in patients with HIT/HITT. Furthermore, NOACs do not cross-react with HIT antibodies(3). That review encompassed data from 56 HIT/HITT patients subsequently treated with NOACs. Data were derived from 3 studies and 8 case reports. Mean age of the 56 patients was 70, twenty four had HIT, and thirty two had HITT. At the time of HIT/HITT diagnosis a nonheparin parenteral agent was initiated in 42, and the remaining 14 transitioned to NOACs straightaway. The NOACS used in the 56 patients were rivaroxaban, apixaban, and dabigatran in 54%, 29%, and 18% of cases, respectively. There were only 2 instances of recurrent thrombosis with NOAC therapy. Major bleeding occurred in 3 patients who did not appear to be on NOAC therapy at the time of the bleed.
References
(1) Prince M., Wenham T
Heparin-induced thrombocytopemia
Postgrad Med J 2018;94:453-547
(2)Linkins L-A., Dans AL., Moores LK et al
American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines
CHEST 2012;141(2 suppl) e4958-5308
(3) Trands PN., Trans M-H
Emerging role of direct oral anticoagulants in the management of heparin-induced thrombocytopenia
Clinical and Applied Thrombosis/Hemostasis 2018;24:201-209
A point of view:
Diuretics and many dietary components significantly increase the risk of uric acid stone formation--Our major concern.
We read with interest and applauded the authors of the review article that mentions adjustment of potential pathophysiologic defects by pharmacotherapy and strongly recommends dietary modification for the prevention of uric stone recurrence (1).
Two thirds of urate excretion occurs at the kidney, the remainder being excreted by the gut. Earlier studies have suggested that the urate is almost fully reabsorbed and that the urate excreted by the kidney is the result of tubular secretion. But more recent data suggests that secretion plays little part, and that excreted urate largely represents the filtered urate which escapes reabsorption. (2)
Different diuretics are likely to have different effects on the renal handling of urate, but this has not been critically ascertained; patients receiving more powerful loop diuretics have a higher risk of developing gout than those receiving the weaker thiazides (3)
Conceptually, a visit to a beer garden is dangerous for two reasons, the intake of purine rich food and drinks (beer) and the intake of fructose-rich soft drinks that blocks certain urate transporters that facilitate urate excretion (4).
These are also associated with a number of common situations, such as the metabolic syndrome, which is correctable by changing to a low caloric diet, essential hypertensio...
A point of view:
Diuretics and many dietary components significantly increase the risk of uric acid stone formation--Our major concern.
We read with interest and applauded the authors of the review article that mentions adjustment of potential pathophysiologic defects by pharmacotherapy and strongly recommends dietary modification for the prevention of uric stone recurrence (1).
Two thirds of urate excretion occurs at the kidney, the remainder being excreted by the gut. Earlier studies have suggested that the urate is almost fully reabsorbed and that the urate excreted by the kidney is the result of tubular secretion. But more recent data suggests that secretion plays little part, and that excreted urate largely represents the filtered urate which escapes reabsorption. (2)
Different diuretics are likely to have different effects on the renal handling of urate, but this has not been critically ascertained; patients receiving more powerful loop diuretics have a higher risk of developing gout than those receiving the weaker thiazides (3)
Conceptually, a visit to a beer garden is dangerous for two reasons, the intake of purine rich food and drinks (beer) and the intake of fructose-rich soft drinks that blocks certain urate transporters that facilitate urate excretion (4).
These are also associated with a number of common situations, such as the metabolic syndrome, which is correctable by changing to a low caloric diet, essential hypertension, decompensated heart failure, saturnine gout, which is correctable by lead chelation, and alcohol consumption (3).
Conclusion:
Recently gained insight into the mechanisms of urate transport through tubular cells is the identification of four proteins which act as urate transporters at that level. These are UAT (urate transporter/channel), two members of the of the family of organic anion transporters (OAT1 and OAT3) related to the tubular secretion of urate, and the main protein responsible for tubular reabsorption of urate (URAT1), located at the apical membrane of the proximal tubular cells (5, 6).
However, as we learn to what extent hyperuricaemia associated with diuretics is due to a direct and specific action of these drugs on the tubular wall or whether they act more generally by reducing the vascular volumes, this will undoubtedly increase our understanding of the association (3). Meanwhile, we need to be careful about dietary components which may also be responsible for the menace.
References:
1. Qi Ma,Li Fang,Rui Su et al, Review: Uric acid stones, clinical manifestations and therapeutic considerations. https://pmj.bmj.com/content/early/2018/07/12/postgradmedj-2017-135332
2. Roch-Ramel F, Guisan B. Renal transport of urate in humans. News Physiol Sci1999; 14:80–4.
3. E Pascual, M Perdiguero. Editorial: Gout, diuretics and the kidney. Annals of the Rheumatic diseases. Volume 65, Issue 8
4. H.-J. Anders. Crystal arthritis: SP0125 Renal Handling of Urate and Gout. Annals of Reumatic diseases. Volume 75, Issue Suppl 2
5. Hediger MA, Johnson RJ, Miyazaki H, Endou H. Molecular physiology of urate transport. Physiology (Bethesda) 2005; 20:125–33.
6. Enomoto A, Endou H. Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clin Exp Nephrol2005; 9:195–205.
The secondary syphilis we see today is potentially different from the secondary syphilis which belongs to the era antedating the presently high incidence and prevalence of human immunodeficiency virus (HIV) infection. Sexually active subjects who harbour the coexistence of HIV infection (with attendant immune suppression) and syphilis are also at risk of opportunistic infections such as tuberculosis and cryptococcosis (1)(2)(3). In one HIV-positive patient aged 43, neurosyphilis coexisted with both cryptococcal meningitis and tuberculous meningitis. The cerebrospinal fluid (CSF) was characterised by lymphocyte predominance low glucose and high protein. Furthermore, in the CSF, cryptococcal antigen amounted to 1;640, and the VDRL from the CSF was also reactive. CSF culture grew M. tuberculosis, and this was confirmed by the polymerase chain reaction (1). In another instance, a 37 year old man with past medical history of HIV infection had neurosyphilis coexisting with cryptococcal meningitis. The CSF was characterised by lymphocyte predominance, positive fluorescent treponemal antibody test and cryptococcal antigen titre of 1:640 (2). Another report involved a 40 year old man with coexisting neurosyphilis and cryptococcal meningitis. The CSF showed lymphocyte predominance and high protein concentration. Cryptococcus was cultured from the CSF and both serum serology and CSF were positive for syphilis (3). These anecdotal reports might underestimate the true prevalence of coe...
The secondary syphilis we see today is potentially different from the secondary syphilis which belongs to the era antedating the presently high incidence and prevalence of human immunodeficiency virus (HIV) infection. Sexually active subjects who harbour the coexistence of HIV infection (with attendant immune suppression) and syphilis are also at risk of opportunistic infections such as tuberculosis and cryptococcosis (1)(2)(3). In one HIV-positive patient aged 43, neurosyphilis coexisted with both cryptococcal meningitis and tuberculous meningitis. The cerebrospinal fluid (CSF) was characterised by lymphocyte predominance low glucose and high protein. Furthermore, in the CSF, cryptococcal antigen amounted to 1;640, and the VDRL from the CSF was also reactive. CSF culture grew M. tuberculosis, and this was confirmed by the polymerase chain reaction (1). In another instance, a 37 year old man with past medical history of HIV infection had neurosyphilis coexisting with cryptococcal meningitis. The CSF was characterised by lymphocyte predominance, positive fluorescent treponemal antibody test and cryptococcal antigen titre of 1:640 (2). Another report involved a 40 year old man with coexisting neurosyphilis and cryptococcal meningitis. The CSF showed lymphocyte predominance and high protein concentration. Cryptococcus was cultured from the CSF and both serum serology and CSF were positive for syphilis (3). These anecdotal reports might underestimate the true prevalence of coexistence of neurosyphilis and other meningeal infections in HIV-positive patients. In order to obtain a true measure of this subtype of mixed meningitis, the recommendation to test for cryptococcal meningitis in all cases of suspected tuberculous meningitis evaluated in HIV-positive patients (4) should be extended to include testing for neurosyphilis in all HIV-positive patients with suspected tuberculous meningitis or suspected cryptococcal meningitis.
References
(1) Zamora JA., Espinoza LA., Nwanyanwu RN
Neurosyphilis with concomitant cryptococcal and tuberculous meningitis in a patient with AIDS: report of a unique case
Case reports in Infectious diseases 2017;doi.org/10.1155/2017/410.3558
(2)Swe T., Laurent BP., Shah NN
Concurrent central nervous system infective pathology in a severely immunocompromised patient
Journal of Family Medicine and Primary Care 2016;5:685-687
(3) Silber E., Sonnenberg P., Koornof HJ., Morris L., Saffer D
Dual infective pathology in patients with cryptococcal meningitis
Neurology 1998;51:1213-1215
(4)Thwaites G., Fisher M., Hemingway C., Scott G., Solomon T., Innes J
british Infection society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children
Journal of Infection 2009;59;167-187
While it is true, as the authors assert, that there is limited data on exercise-induced reversal of cardiac remodeling, a recent study suggests that the cardiac effects of sedentary aging(in middle age) can be reversed by exercise training(1). In that study sixty one(48% male) healthy sedentary participants of mean age 53 were randomly assigned to either 2 years of exercise training(n=34) or attention control(control=27). In each subject measurements were taken to evaluate left ventricular stiffness. Maximal oxygen uptake was measured to quantify changes in fitness. Fifty three participants completed the study. Adherence to prescribed exercise sessions was 88% on average. As a result of exercise training left ventricular stiffness was significantly(p=0.0018)reduced(right/ downward shift in the end-diastolic pressure-volume relationships) in comparison with its pre-exercise value. This parameter did not change in the control group. Exercise significantly(p<0.001)increased the left ventricular end diastolic volume , whereas pulmonary capillary wedge pressure was unchanged, thereby generating significantly(p=0.007) greater stroke volume for any given filling pressure. The authors concluded that regular exercise training could provide protection against the future risk of heart failure with preserved ejection fraction by mitigating the risk of increase in cardiac stiffness attributable to a sedentary lifestyle(1). Accordingly, although we cannot influence the natu...
While it is true, as the authors assert, that there is limited data on exercise-induced reversal of cardiac remodeling, a recent study suggests that the cardiac effects of sedentary aging(in middle age) can be reversed by exercise training(1). In that study sixty one(48% male) healthy sedentary participants of mean age 53 were randomly assigned to either 2 years of exercise training(n=34) or attention control(control=27). In each subject measurements were taken to evaluate left ventricular stiffness. Maximal oxygen uptake was measured to quantify changes in fitness. Fifty three participants completed the study. Adherence to prescribed exercise sessions was 88% on average. As a result of exercise training left ventricular stiffness was significantly(p=0.0018)reduced(right/ downward shift in the end-diastolic pressure-volume relationships) in comparison with its pre-exercise value. This parameter did not change in the control group. Exercise significantly(p<0.001)increased the left ventricular end diastolic volume , whereas pulmonary capillary wedge pressure was unchanged, thereby generating significantly(p=0.007) greater stroke volume for any given filling pressure. The authors concluded that regular exercise training could provide protection against the future risk of heart failure with preserved ejection fraction by mitigating the risk of increase in cardiac stiffness attributable to a sedentary lifestyle(1). Accordingly, although we cannot influence the natural history of diastolic heart failure we can mitigate the risk of its occurence.
References
Howden EJ., Sarma S., Lawley JS., Opondo M., Cornwell W., Stoller D et al
Reversing the cardiac effects of sedentary aging in middle age-A randomised controlled trial
Circulation 2018;137:DOI 10.1161/CIRCULATIONAHA.117.030617
Improving communication in decision-making is a worthy goal and the choice of words is crucial. Sayma and colleagues (1) have not considered the implications of some of their choices.
Firstly, throughout the article they have used the word ‘advanced’ when describing decisions and care plans. This is a common misspelling but such issues are not superior formats but are care plans and decisions made in advance. Secondly, the authors mention ‘ceilings of care’ but do not explain that there are no ethical or legal permissions that allow care to be limited. This term is often misused when what is meant is a limit to treatment options. Finally the use of ‘escalation’ in care plans has been shown to be threatening to patients.(2) The term is too often used by clinicians without considering how this might be considered by patients.
None of this should not detract from the value of the information provided during the study, but perhaps the authors will think carefully in future about their choice of words.
Claud Regnard
References
1. Sayma M et al. Improving the use of treatment escalation plans: a quality improvement study. Postgrad Med J, 2018; doi: 10.1136/postgradmedj-2018-135699.
2. Fritz Z, Fudd JP. Development of the Universal Form of Treatment Options (UFTO) as an alternative to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders: a cross disciplinary approach. J Evaluation in Clinical Practice 2014; 21: 109-117.
I agree with the authors of this excellent review that blood pressure(BP) measurement is often performed carelessly, and this is true both in primary and in secondary care. Although both doctors and nurses are responsible for this state of affairs, appropriately trained and dedicated(in terms of their job description) nurse practitioners are the ones who would be best placed to comply with the requirements for correct blood pressure measurement within "real world" time constraints(1). My proposal is to allocate a 10-15 minute slot for the nurse practitioner to measure the blood pressure in the relaxed environment of her own consulting room. Thereafter she can hand the patient over to the doctor to fulfil his own 10 minute or so time slot.
Choice of diuretic medication for management of hypertension is the other issue specially relevant to the elderly. Although diuretics of first choice for antihypertensive treatment are typically either thiazides or indapamide, what needs to be recognised is that susceptibility to diuretic-related hyponatraemia involving those two drug subclasses is uniquely age-related, patients aged 60 or more being the ones most vulnerable to this complication(2)(3)(4)(5)(6). It is even conceivable that symptoms of drug-related hyponatraemia such as falls(2)(3) , might, on occasion, be misattributed to attainment of goal blood pressure, even if that target blood pressure is a modest one, with the consequence that antihypertensive...
I agree with the authors of this excellent review that blood pressure(BP) measurement is often performed carelessly, and this is true both in primary and in secondary care. Although both doctors and nurses are responsible for this state of affairs, appropriately trained and dedicated(in terms of their job description) nurse practitioners are the ones who would be best placed to comply with the requirements for correct blood pressure measurement within "real world" time constraints(1). My proposal is to allocate a 10-15 minute slot for the nurse practitioner to measure the blood pressure in the relaxed environment of her own consulting room. Thereafter she can hand the patient over to the doctor to fulfil his own 10 minute or so time slot.
Choice of diuretic medication for management of hypertension is the other issue specially relevant to the elderly. Although diuretics of first choice for antihypertensive treatment are typically either thiazides or indapamide, what needs to be recognised is that susceptibility to diuretic-related hyponatraemia involving those two drug subclasses is uniquely age-related, patients aged 60 or more being the ones most vulnerable to this complication(2)(3)(4)(5)(6). It is even conceivable that symptoms of drug-related hyponatraemia such as falls(2)(3) , might, on occasion, be misattributed to attainment of goal blood pressure, even if that target blood pressure is a modest one, with the consequence that antihypertensive medication may be inappropriately discontinued.
References
(1) Jolobe, OMP
Mythmaking in the measurement of blood pressure
European Journal of Internal Medicine 2014;25:e11
(2)Liamis G., Filippatos TD., Elisaf MS
Thiazide associated hyponatremia in the elderly;what the clinician needs to know
Journal of geriatric cardiology 2016;13:175-182
(3) Barber J., McKeever TM., McDowell SE., Clayton JA., Ferner RE., Gordon RD et al
A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?
BJCP 2014;79:566-577
(4) Burst V., Grundmann F., Kubacki T., Greenberg A., Becker I., Rudolf D., Verbalis J
Thiazide-associated hyponatremia, Report of hyponatremia registry: An observational multicenter International Study
Am J Nephrology 2017;45:420-430
(5) Chapman MD., Hanrahan R., McEwen J., Marley JE
Hyponatraemia and hypokalaemia due to indapamide
Med J Aust 2002;176:219-221
(6)Yong TY., Huang JE., Kau SY., Li JY
Severe hyponatremia and other electrolyte disturbances associated with indapamide
Curr Drug Saf 2011;6:134-137
Your recent report titled “Career specialty choices of UK medical graduates of 2015 compared with earlier cohorts: questionnaire surveys”(1) provided a thought-provoking read.
As highlighted in your report, the uptake in training for specialties such as general practice continues to remain low. I strongly agree that in order to address this it is necessary to identify the factors that determine career choice in junior doctors. Furthermore, to encourage doctors to peruse undersubscribed specialties, it may be useful to identify the stage in training that the foundations of career choice are made. This may provide an opportunity to spark interest about these low uptake specialties in doctors who are still open minded about their future career.
Your report demonstrates that even very early on in training, many doctors have a definite choice about their future specialty (1). Data collected from students at Brighton and Sussex medical school demonstrated that specialty choice is highly influenced by student’s experiences at medical school (2). I am a fourth year medical student, currently rotating through these various specialty placements and beginning to realistically consider my own personal career options. I too believe that the clinical phase of medical school may hold a unique window to motivate students to become interested in those undersubscribed specialties.
Earlier this year a cohort study at the University of Dundee showed t...
Your recent report titled “Career specialty choices of UK medical graduates of 2015 compared with earlier cohorts: questionnaire surveys”(1) provided a thought-provoking read.
As highlighted in your report, the uptake in training for specialties such as general practice continues to remain low. I strongly agree that in order to address this it is necessary to identify the factors that determine career choice in junior doctors. Furthermore, to encourage doctors to peruse undersubscribed specialties, it may be useful to identify the stage in training that the foundations of career choice are made. This may provide an opportunity to spark interest about these low uptake specialties in doctors who are still open minded about their future career.
Your report demonstrates that even very early on in training, many doctors have a definite choice about their future specialty (1). Data collected from students at Brighton and Sussex medical school demonstrated that specialty choice is highly influenced by student’s experiences at medical school (2). I am a fourth year medical student, currently rotating through these various specialty placements and beginning to realistically consider my own personal career options. I too believe that the clinical phase of medical school may hold a unique window to motivate students to become interested in those undersubscribed specialties.
Earlier this year a cohort study at the University of Dundee showed that positive experience in medical school was the biggest influencer in career choice and that almost half of students were following the career consistent with their first choice at final year, highlighting the longevity of these positive experiences (3).
Therefore, in order to encourage uptake for training in specialties such as general practice, targeting students who have not yet left medical school (and therefore are more likely to be more open minded about career choice) may be an effective recruitment strategy. Furthermore, this strategy could focus on establishing a positive experience for medical students whilst on clinical placements.
Considering this, whilst current recruitment strategies such as salary supplements for GP trainees in low-recruitment areas are no doubt important, they may be missing some of their most impressionable audience. By developing a broader interest in GP specialty during medical school through positive clinical experiences, students may be more motivated to tackle the issues within general practice and therefore more likely to take up in training in areas where historically recruitment has been low.
Taking a broader, grass-roots approach to recruitment of low uptake specialties may result in more final-year students with realistic and long-standing career aspirations within these specialties. Building on the conclusions in the report discussed here, medical school experience is a known determining factor in the career choice of junior doctors. Therefore, it may be important to identify the factors that make clinical placement experience positive or negative, in order to improve placement experience and ultimately promote uptake of specific specialties, such as general practice.
1. Lambert TW, Smith F, Goldacre MJ. Career specialty choices of UK medical graduates of 2015 compared with earlier cohorts: questionnaire surveys. Postgrad Med J [Internet]. 2018;postgradmedj – 2017–135309.
2. Woolf K, Elton C, Newport M. The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study. BMC Med Educ. 2015;15:46.
3. McNaughton E, Riches J, Harrison G, Mires G, MacEwen C. What factors influenced the choice of medical specialty for doctors surveyed in the final year at medical school and again having entered their specialty training destination? Postgrad Med J [Internet]. 2018;0(0):postgradmedj – 2017–135370.
The judgment that imaging studies were over-utilised (1) should not be based on the degree of compliance with the Wells clinical decision rule (CDR), given the fact that the Wells score is not necessarily the optimal one for PE. In a study which compared 7 CDRs, namely, the Wells score, simplified Wells score, original Geneva score, revised Geneva score, Charlotte score and the Pisa model, diagnostic accuracy amounted to 0.44, 0.61, and 0.76 for simplified Wells score, Wells score, and Pisa model, respectively (2). The Wells score was tested in 598 primary care patients presenting with symptoms including cough, unexpected or sudden dyspnoea, deterioration in existing dyspnoea, and pleuritic pain, singly or in combination. These patients were referred to secondary care with suspected PE, where they were subsequently rigorously evaluated and investigated according to hospital guidelines. The diagnosis of PE was subsequently confirmed in 73 cases. However, in as many as 44 of those cases where PE was ruled out, the presenting Wells score amounted to >4 points (3), a score that is taken to signify "PE likely" in the simplified Wells score. In the evaluation of PE diagnostic confusion is compounded by the fact that PE can be an incidental finding, for example, during CT imaging in the oncological context (4). In the latter study, 25% of 52 patients with incidental PE had no PE-related symptoms (4). In the entire group of 52 patients with incidental PE, eight had m...
Show MoreThe terminology of the chest x-ray report can, indeed, impact on the timeliness of the eventual validation of the diagnosis of pulmonary tuberculosis, as shown by the case report of a 75 year old man who was originally admitted with fever and backache. Chest x-ray showed "fibronodular infiltration of the left apex of the lung" (1). On the basis of magnetic resonance imaging, backache was attributed to osteomyelitis, and he was treated with antibiotics, and there was no "work-up" of the fibronodular infiltration of the lung apex. Over a period of two weeks fever persisted, and he became pancytopenic. However, it was only after a further 3 weeks, when pancytopenia became more severe, that bone marrow aspiration and bone marrow biopsy was performed. The latter showed epitheloid granulomas and acid fast bacilli. Polymerase chain reaction analysis of the bone marrow specimens was positive for M tuberculosis DNA, and his sputum was culture positive for M tuberculosis. Although antituberculous chemotherapy was initiated immediately after the bone marrow results he died 3 days after commencing treatment (2).
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Arguably, if the term "tuberculosis" had been used to qualify the nodular infiltration seen on chest x-ray, that would have raised the index of suspicion for tuberculosis (TB), and computed tomography might have been utilised to characterise the nodularity as being TB-related (2). Two weeks later, in the light of that heightene...
Given the fact that the risk of heparin-induced thrombocytopenia (HIT) is higher with prolonged therapy, the new oral anticoagulants (NOACs) might have a role in shortening the duration of low molecular weight heparin (LMWH) thromboprophylaxis in cancer patients from its currently recommended minimum of 3 months (1) to a much shorter duration by facilitating a transition to NOACSs( 2). That strategy might mitigate the risk of occurrence of HIT.
Show MoreCurrently, international guidelines recommend LMWH instead of warfarin for management of cancer-related venous thromboembolism (1), but the duration of that management strategy puts patients at risk of HIT, with all its attendant consequences. In an open-label, noninferiority trial, patients with cancer-associated venous thromboembolism were randomly assigned to LMWH for at least 5 days followed by oral edoxaban (60 mg/day) (edoxaban group) or subcutaneous dalteparin at an appropriate dose. Treatment duration in both cases was at least 6 months. In that study, recurrent venous thromboembolism occurred in 7.9% of the edoxaban group vs. 11.3% of the dalteparin group (P=0.09). Major bleeding occurred in 6.9% of the edoxaban group vs. 4% of the dalteparin group (P=0.04). The increase in major bleeding was principally attributable to upper gastrointestinal bleeding in patients who had gastric cancer (2). A criticism of that study is that the 60 mg/day of edoxaban is inherently associated with significantly (P=0.03) greater risk of...
In their excellent review the authors drew attention to alternative oral anticoagulants to manage heparin-induced thrombocytopenia(HIT)(1). The American College of Chest Physicians guideline for HIT and HIT-associated thrombosis(HITT) cautions against premature transition to vitamin K antagonist therapy due to significant risk of warfarin-induced skin necrosis or development of venous limb gangrene(2). According to a recent review, the new oral anticoagulants(NOACs) are not burdened with that disadvantage, and their rapid onset of action generates a smooth transition to forward anticoagulation in patients with HIT/HITT. Furthermore, NOACs do not cross-react with HIT antibodies(3). That review encompassed data from 56 HIT/HITT patients subsequently treated with NOACs. Data were derived from 3 studies and 8 case reports. Mean age of the 56 patients was 70, twenty four had HIT, and thirty two had HITT. At the time of HIT/HITT diagnosis a nonheparin parenteral agent was initiated in 42, and the remaining 14 transitioned to NOACs straightaway. The NOACS used in the 56 patients were rivaroxaban, apixaban, and dabigatran in 54%, 29%, and 18% of cases, respectively. There were only 2 instances of recurrent thrombosis with NOAC therapy. Major bleeding occurred in 3 patients who did not appear to be on NOAC therapy at the time of the bleed.
Show MoreReferences
(1) Prince M., Wenham T
Heparin-induced thrombocytopemia
Postgrad Med J 2018;94:453-547
(2)Linkins L-A....
A point of view:
Show MoreDiuretics and many dietary components significantly increase the risk of uric acid stone formation--Our major concern.
We read with interest and applauded the authors of the review article that mentions adjustment of potential pathophysiologic defects by pharmacotherapy and strongly recommends dietary modification for the prevention of uric stone recurrence (1).
Two thirds of urate excretion occurs at the kidney, the remainder being excreted by the gut. Earlier studies have suggested that the urate is almost fully reabsorbed and that the urate excreted by the kidney is the result of tubular secretion. But more recent data suggests that secretion plays little part, and that excreted urate largely represents the filtered urate which escapes reabsorption. (2)
Different diuretics are likely to have different effects on the renal handling of urate, but this has not been critically ascertained; patients receiving more powerful loop diuretics have a higher risk of developing gout than those receiving the weaker thiazides (3)
Conceptually, a visit to a beer garden is dangerous for two reasons, the intake of purine rich food and drinks (beer) and the intake of fructose-rich soft drinks that blocks certain urate transporters that facilitate urate excretion (4).
These are also associated with a number of common situations, such as the metabolic syndrome, which is correctable by changing to a low caloric diet, essential hypertensio...
The secondary syphilis we see today is potentially different from the secondary syphilis which belongs to the era antedating the presently high incidence and prevalence of human immunodeficiency virus (HIV) infection. Sexually active subjects who harbour the coexistence of HIV infection (with attendant immune suppression) and syphilis are also at risk of opportunistic infections such as tuberculosis and cryptococcosis (1)(2)(3). In one HIV-positive patient aged 43, neurosyphilis coexisted with both cryptococcal meningitis and tuberculous meningitis. The cerebrospinal fluid (CSF) was characterised by lymphocyte predominance low glucose and high protein. Furthermore, in the CSF, cryptococcal antigen amounted to 1;640, and the VDRL from the CSF was also reactive. CSF culture grew M. tuberculosis, and this was confirmed by the polymerase chain reaction (1). In another instance, a 37 year old man with past medical history of HIV infection had neurosyphilis coexisting with cryptococcal meningitis. The CSF was characterised by lymphocyte predominance, positive fluorescent treponemal antibody test and cryptococcal antigen titre of 1:640 (2). Another report involved a 40 year old man with coexisting neurosyphilis and cryptococcal meningitis. The CSF showed lymphocyte predominance and high protein concentration. Cryptococcus was cultured from the CSF and both serum serology and CSF were positive for syphilis (3). These anecdotal reports might underestimate the true prevalence of coe...
Show MoreWhile it is true, as the authors assert, that there is limited data on exercise-induced reversal of cardiac remodeling, a recent study suggests that the cardiac effects of sedentary aging(in middle age) can be reversed by exercise training(1). In that study sixty one(48% male) healthy sedentary participants of mean age 53 were randomly assigned to either 2 years of exercise training(n=34) or attention control(control=27). In each subject measurements were taken to evaluate left ventricular stiffness. Maximal oxygen uptake was measured to quantify changes in fitness. Fifty three participants completed the study. Adherence to prescribed exercise sessions was 88% on average. As a result of exercise training left ventricular stiffness was significantly(p=0.0018)reduced(right/ downward shift in the end-diastolic pressure-volume relationships) in comparison with its pre-exercise value. This parameter did not change in the control group. Exercise significantly(p<0.001)increased the left ventricular end diastolic volume , whereas pulmonary capillary wedge pressure was unchanged, thereby generating significantly(p=0.007) greater stroke volume for any given filling pressure. The authors concluded that regular exercise training could provide protection against the future risk of heart failure with preserved ejection fraction by mitigating the risk of increase in cardiac stiffness attributable to a sedentary lifestyle(1). Accordingly, although we cannot influence the natu...
Show MoreImproving communication in decision-making is a worthy goal and the choice of words is crucial. Sayma and colleagues (1) have not considered the implications of some of their choices.
Firstly, throughout the article they have used the word ‘advanced’ when describing decisions and care plans. This is a common misspelling but such issues are not superior formats but are care plans and decisions made in advance. Secondly, the authors mention ‘ceilings of care’ but do not explain that there are no ethical or legal permissions that allow care to be limited. This term is often misused when what is meant is a limit to treatment options. Finally the use of ‘escalation’ in care plans has been shown to be threatening to patients.(2) The term is too often used by clinicians without considering how this might be considered by patients.
None of this should not detract from the value of the information provided during the study, but perhaps the authors will think carefully in future about their choice of words.
Claud Regnard
References
1. Sayma M et al. Improving the use of treatment escalation plans: a quality improvement study. Postgrad Med J, 2018; doi: 10.1136/postgradmedj-2018-135699.
2. Fritz Z, Fudd JP. Development of the Universal Form of Treatment Options (UFTO) as an alternative to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders: a cross disciplinary approach. J Evaluation in Clinical Practice 2014; 21: 109-117.
I agree with the authors of this excellent review that blood pressure(BP) measurement is often performed carelessly, and this is true both in primary and in secondary care. Although both doctors and nurses are responsible for this state of affairs, appropriately trained and dedicated(in terms of their job description) nurse practitioners are the ones who would be best placed to comply with the requirements for correct blood pressure measurement within "real world" time constraints(1). My proposal is to allocate a 10-15 minute slot for the nurse practitioner to measure the blood pressure in the relaxed environment of her own consulting room. Thereafter she can hand the patient over to the doctor to fulfil his own 10 minute or so time slot.
Show MoreChoice of diuretic medication for management of hypertension is the other issue specially relevant to the elderly. Although diuretics of first choice for antihypertensive treatment are typically either thiazides or indapamide, what needs to be recognised is that susceptibility to diuretic-related hyponatraemia involving those two drug subclasses is uniquely age-related, patients aged 60 or more being the ones most vulnerable to this complication(2)(3)(4)(5)(6). It is even conceivable that symptoms of drug-related hyponatraemia such as falls(2)(3) , might, on occasion, be misattributed to attainment of goal blood pressure, even if that target blood pressure is a modest one, with the consequence that antihypertensive...
Dear authors,
Your recent report titled “Career specialty choices of UK medical graduates of 2015 compared with earlier cohorts: questionnaire surveys”(1) provided a thought-provoking read.
As highlighted in your report, the uptake in training for specialties such as general practice continues to remain low. I strongly agree that in order to address this it is necessary to identify the factors that determine career choice in junior doctors. Furthermore, to encourage doctors to peruse undersubscribed specialties, it may be useful to identify the stage in training that the foundations of career choice are made. This may provide an opportunity to spark interest about these low uptake specialties in doctors who are still open minded about their future career.
Your report demonstrates that even very early on in training, many doctors have a definite choice about their future specialty (1). Data collected from students at Brighton and Sussex medical school demonstrated that specialty choice is highly influenced by student’s experiences at medical school (2). I am a fourth year medical student, currently rotating through these various specialty placements and beginning to realistically consider my own personal career options. I too believe that the clinical phase of medical school may hold a unique window to motivate students to become interested in those undersubscribed specialties.
Earlier this year a cohort study at the University of Dundee showed t...
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